![conference banner](/images/conference-banner.jpeg)
Abstract
Leukemias, as other cancers, bear several genetic alterations of tumor-related genes, such as point mutations, translocations, epigenetic modifications, often accompanied by gene amplification or inactivation. The identification of tumor-related genes provides considerable insight into the biology of leukemias and opens the way to more specific pharmacological treatments. These genes comprise several ion channels and pumps, as the transport mechanisms associated with volume control, proliferation and apoptosis are often altered in cancers. In leukemic cells, such changes are observed as early as the stem cell stage. Ion channels can regulate other malignant features, such as lack of differentiation, increased migratory and invasive phenotype and chemoresistance. The role of certain voltage-gated K+ channels, such as Kv11.1 (also known as hERG1) can be largely attributed to modulation of cell adhesion to the extracellular matrix (ECM). Kv11.1 exerts pleiotropic regulatory effects by forming multiprotein membrane complexes with integrin receptors in both acute myeloid leukemias (AML) and acute lymphoblastic leukemias (ALL). By recruiting growth factor and chemokine receptors, these complexes form signaling hubs that control neoplastic progression. Work in mice shows that blocking Kv11.1 has a protective effect in acute leukemias. Ion channels are most promising targets for anti-leukemic therapy, because of their accessibility from the extracellular side and the thorough understanding of their pharmacology. In ALL cells, Kv11.1 inhibitors abrogate the protective effect of bone marrow stromal cells and enhance the cytotoxicity of some common antileukemic drugs. Hence, ion channel modulators could overcome chemoresistance in acute leukemias, a major hindrance to therapeutic success.
Keywords: Chemoresistance, combined treatment, Kv11.1, ion channels, leukemia, therapy, antileukemic drugs, stroma, mechanisms of channel block, conformational states
Current Medicinal Chemistry
Title: Targeting Ion Channels in Leukemias: A New Challenge for Treatment
Volume: 19 Issue: 5
Author(s): A. Arcangeli, S. Pillozzi and A. Becchetti
Affiliation:
Keywords: Chemoresistance, combined treatment, Kv11.1, ion channels, leukemia, therapy, antileukemic drugs, stroma, mechanisms of channel block, conformational states
Abstract: Leukemias, as other cancers, bear several genetic alterations of tumor-related genes, such as point mutations, translocations, epigenetic modifications, often accompanied by gene amplification or inactivation. The identification of tumor-related genes provides considerable insight into the biology of leukemias and opens the way to more specific pharmacological treatments. These genes comprise several ion channels and pumps, as the transport mechanisms associated with volume control, proliferation and apoptosis are often altered in cancers. In leukemic cells, such changes are observed as early as the stem cell stage. Ion channels can regulate other malignant features, such as lack of differentiation, increased migratory and invasive phenotype and chemoresistance. The role of certain voltage-gated K+ channels, such as Kv11.1 (also known as hERG1) can be largely attributed to modulation of cell adhesion to the extracellular matrix (ECM). Kv11.1 exerts pleiotropic regulatory effects by forming multiprotein membrane complexes with integrin receptors in both acute myeloid leukemias (AML) and acute lymphoblastic leukemias (ALL). By recruiting growth factor and chemokine receptors, these complexes form signaling hubs that control neoplastic progression. Work in mice shows that blocking Kv11.1 has a protective effect in acute leukemias. Ion channels are most promising targets for anti-leukemic therapy, because of their accessibility from the extracellular side and the thorough understanding of their pharmacology. In ALL cells, Kv11.1 inhibitors abrogate the protective effect of bone marrow stromal cells and enhance the cytotoxicity of some common antileukemic drugs. Hence, ion channel modulators could overcome chemoresistance in acute leukemias, a major hindrance to therapeutic success.
Export Options
About this article
Cite this article as:
Arcangeli A., Pillozzi S. and Becchetti A., Targeting Ion Channels in Leukemias: A New Challenge for Treatment, Current Medicinal Chemistry 2012; 19 (5) . https://dx.doi.org/10.2174/092986712798992093
DOI https://dx.doi.org/10.2174/092986712798992093 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Multitarget-Directed Ligands: Innovative Chemical Probes and Therapeutic Tools Against Alzheimer's Disease
Current Topics in Medicinal Chemistry Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases
Current Gene Therapy Gene Therapy Targeting Nuclear Factor-κB: Towards Clinical Application in Inflammatory Diseases and Cancer
Current Gene Therapy Editorial (Thematic Issue: Mechanisms of Cancer Stem Cell Resistance to Chemotherapy)
Current Signal Transduction Therapy A Nanostructured Silica-Lipid Hybrid to Facilitate Oral SN-38-based Chemotherapy
Drug Delivery Letters Recent Advances in Optical Cancer Imaging of EGF Receptors
Current Medicinal Chemistry Epithelial-Mesenchymal Transition: Implications in Cancer Progression and Metastasis
Current Pharmaceutical Biotechnology An Integrated Feature Selection Algorithm for Cancer Classification using Gene Expression Data
Combinatorial Chemistry & High Throughput Screening Novel Approaches to Cancer Therapy Using Oncolytic Viruses
Current Molecular Medicine Nitric Oxide in Cancer Therapeutics: Interaction with Cytotoxic Chemotherapy
Current Pharmaceutical Design The Applicability of mTOR Inhibition in Solid Tumors
Current Cancer Drug Targets Nano-pharmaceutical Formulations for Targeted Drug Delivery against HER2 in Breast Cancer
Current Cancer Drug Targets Targeting the BRCA1/2 Tumor Suppressors
Current Drug Targets Cancer Nanotechnology - Prospects for Cancer Diagnostics and Therapy
Current Cancer Therapy Reviews Decoding the Knots of Initiation of Oncogenic Epithelial-Mesenchymal Transition in Tumor Progression
Current Cancer Drug Targets Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer
Current Pharmaceutical Design Lipid Metabolism and Mitochondria: Cross Talk in Cancer
Current Drug Targets Pioglitazone and Cancer: Angel or Demon?
Current Pharmaceutical Design Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise
Current Pharmaceutical Design Detection of Predictive Markers for Therapeutic Stratification of Salivary Glands Tumors
Current Drug Targets